New methodologies are proposed utilizing a) hybrid Chinese hamster ovary cells containing particular human chromosomes providing human cell surface antigenic markers; b) selection methods for isolating specific mutants which have lost particular markers; c) recombinant DNA techniques for identifying specific, mapped human DNA sequences that may be lost as a result of mutation; and d) a combination of these various methodologies to detect and quantitate the frequency of translocations. These various operations will be combined in a single procedure which promises to analyze the results of exposure of these cells to physical, chemical and biological agents in terms of each of the principal mutagenic actions known to be important in human diseases: localized mutations, small deletions, large deletions, chromosome loss and translocations. In addition, this approach promises to yield quantitative measurement of the dose response of each mutagen for each type of lesion with a sensitivity many times greater than previously achieved. It is also proposed to apply these methodologies for detection of situations representing human health hazards and for study of aspects of the mutagenic process.